The gut microbiome regulates a number of homeostatic mechanisms in the healthy host including immune function and gut barrier protection. Loss of normal gut microbial structure and function has been ...associated with diseases as diverse as Clostridioides difficile infection, asthma, and epilepsy. Recent evidence has also demonstrated a link between the gut microbiome and sepsis. In this review, we focus on three key areas of the interaction between the gut microbiome and sepsis. First, prior to sepsis onset, gut microbiome alteration increases sepsis susceptibility through several mechanisms, including (a) allowing for expansion of pathogenic intestinal bacteria, (b) priming the immune system for a robust pro-inflammatory response, and (c) decreasing production of beneficial microbial products such as short-chain fatty acids. Second, once sepsis is established, gut microbiome disruption worsens and increases susceptibility to end-organ dysfunction. Third, there is limited evidence that microbiome-based therapeutics, including probiotics and selective digestive decontamination, may decrease sepsis risk and improve sepsis outcomes in select patient populations, but concerns about safety have limited uptake. Case reports of a different microbiome-based therapy, fecal microbiota transplantation, have shown correlation with gut microbial structure restoration and decreased inflammatory response, but these results require further validation. While much of the evidence linking the gut microbiome and sepsis has been established in pre-clinical studies, clinical evidence is lacking in many areas. To address this, we outline a potential research agenda for further investigating the interaction between the gut microbiome and sepsis.
OBJECTIVES:To determine mortality rates among adults with critical illness from coronavirus disease 2019.
DESIGN:Observational cohort study of patients admitted from March 6, 2020, to April 17, 2020.
...SETTING:Six coronavirus disease 2019 designated ICUs at three hospitals within an academic health center network in Atlanta, Georgia, United States.
PATIENTS:Adults greater than or equal to 18 years old with confirmed severe acute respiratory syndrome-CoV-2 disease who were admitted to an ICU during the study period.
INTERVENTIONS:None.
MEASUREMENTS AND MAIN RESULTS:Among 217 critically ill patients, mortality for those who required mechanical ventilation was 35.7% (59/165), with 4.8% of patients (8/165) still on the ventilator at the time of this report. Overall mortality to date in this critically ill cohort is 30.9% (67/217) and 60.4% (131/217) patients have survived to hospital discharge. Mortality was significantly associated with older age, lower body mass index, chronic renal disease, higher Sequential Organ Failure Assessment score, lower PaO2/FIO2 ratio, higher D-dimer, higher C-reactive protein, and receipt of mechanical ventilation, vasopressors, renal replacement therapy, or vasodilator therapy.
CONCLUSIONS:Despite multiple reports of mortality rates exceeding 50% among critically ill adults with coronavirus disease 2019, particularly among those requiring mechanical ventilation, our early experience indicates that many patients survive their critical illness.
OBJECTIVES:Increasing time to mechanical ventilation and high-flow nasal cannula use may be associated with mortality in coronavirus disease 2019. We examined the impact of time to intubation and use ...of high-flow nasal cannula on clinical outcomes in patients with coronavirus disease 2019.
DESIGN:Retrospective cohort study.
SETTING:Six coronavirus disease 2019-specific ICUs across four university-affiliated hospitals in Atlanta, Georgia.
PATIENTS:Adults with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection who received high-flow nasal cannula or mechanical ventilation.
INTERVENTIONS:None.
MEASUREMENTS AND MAIN RESULTS:Among 231 patients admitted to the ICU, 109 (47.2%) were treated with high-flow nasal cannula and 97 (42.0%) were intubated without preceding high-flow nasal cannula use. Of those managed with high-flow nasal cannula, 78 (71.6%) ultimately received mechanical ventilation. In total, 175 patients received mechanical ventilation; 44.6% were female, 66.3% were Black, and the median age was 66 years (interquartile range, 56–75 yr). Seventy-six patients (43.4%) were intubated within 8 hours of ICU admission, 57 (32.6%) between 8 and 24 hours of admission, and 42 (24.0%) greater than or equal to 24 hours after admission. Patients intubated within 8 hours were more likely to have diabetes, chronic comorbidities, and higher admission Sequential Organ Failure Assessment scores. Mortality did not differ by time to intubation (≤ 8 hr38.2%; 8–24 hr31.6%; ≥ 24 hr38.1%; p = 0.7), and there was no association between time to intubation and mortality in adjusted analysis. Similarly, there was no difference in initial static compliance, duration of mechanical ventilation, or ICU length of stay by timing of intubation. High-flow nasal cannula use prior to intubation was not associated with mortality.
CONCLUSIONS:In this cohort of critically ill patients with coronavirus disease 2019, neither time from ICU admission to intubation nor high-flow nasal cannula use were associated with increased mortality. This study provides evidence that coronavirus disease 2019 respiratory failure can be managed similarly to hypoxic respiratory failure of other etiologies.
Deep-seated Candida spp. infections may necessitate extended durations of antifungal therapy. Increasing resistance to first-line antifungals threatens the most common options for long-term ...treatment. In this issue, Ponta et al. (Antimicrob Agents Chemother 68:e00750-24, 2024, https://doi.org/10.1128/aac.00750-24) present cases in which they used rezafungin, a novel long-acting echinocandin antifungal, for extended durations. While excellent clinical evidence supports the short-term safety of rezafungin, these cases demonstrate that rezafungin may additionally have a role in long-term suppressive therapy for antifungal-resistant Candida spp. infections.
The emergence of SARS-CoV-2 variants with mutations in the spike protein is raising concerns about the efficacy of infection- or vaccine-induced antibodies. We compared antibody binding and live ...virus neutralization of sera from naturally infected and Moderna-vaccinated individuals against two SARS-CoV-2 variants: B.1 containing the spike mutation D614G and the emerging B.1.351 variant containing additional spike mutations and deletions. Sera from acutely infected and convalescent COVID-19 patients exhibited a 3-fold reduction in binding antibody titers to the B.1.351 variant receptor-binding domain of the spike protein and a 3.5-fold reduction in neutralizing antibody titers against SARS-CoV-2 B.1.351 variant compared to the B.1 variant. Similar results were seen with sera from Moderna-vaccinated individuals. Despite reduced antibody titers against the B.1.351 variant, sera from infected and vaccinated individuals containing polyclonal antibodies to the spike protein could still neutralize SARS-CoV-2 B.1.351, suggesting that protective humoral immunity may be retained against this variant.
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•Antibodies from infected and vaccinated individuals bind to the B.1.351 RBD•Convalescent sera through eight months can neutralize the B.1.351 variant•Serum from vaccinated individuals retains neutralization against the B.1.351 variant
In this study, Edara et al. (2021) report that, despite reduced antibody binding to the B.1.351 RBD, sera from infected (acute and convalescent) and Moderna (mRNA-1273)-vaccinated individuals were still able to neutralize the SARS-CoV-2 B.1.351 variant, suggesting that protective humoral immunity may be retained against this variant.
In this report, the evolution of SARS-CoV-2 in response to immunologic and monoclonal-antibody pressure is explored in five patients with B-cell deficiency.
Abstract
There is increasing evidence for the importance of the gut microbiome in human health and disease. Traditional and modern technologies - from cell culture to next generation sequencing - ...have facilitated these advances in knowledge. Each of the tools employed in measuring the microbiome exhibits unique capabilities that may be leveraged for clinical diagnostics. However, much still needs to be done to standardize the language and metrics by which a microbiome is characterized. Here we review the capabilities of gut microbiome-based diagnostics, review selected examples, and discuss the outlook towards clinical application.
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